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Biomedical subjects

K Yazawa

Publications and source records attributed to K Yazawa.

At least 127 records · Page 7Linked to original sources
PubMed1994

Complete discrimination of docosahexaenoate from arachidonate by 85 kDa cytosolic phospholipase A2 during the hydrolysis of diacyl- and alkenylacylglycerophosphoethanolamine.

In our previous report (Shikano, M., Masuzawa, Y. and Yazawa, K. (1993) J. Immunol. 150, 3525-3533), we described that the enrichment of docosahexaenoic acid (DHA, 22:6(n - 3)) reduces both arachidonic acid (AA, 20:4(n - 6)) release and platelet-activating factor (PAF) synthesis in human eosinophilic leukemia cells, Eol-1. Since no DHA release was observed in response to Ca-ionophore stimulation, we presumed that the phospholipase A2 (PLA2) responsible for AA release and PAF synthesis can not hydrolyze the DHA moiety of phospholipids. In the present paper, we examined whether DHA-containing diacyl- and alkenylacylglycerophosphoethanolamine (DHA-diacylGPE and DHA-alkenylacyGPE) are susceptible to the action of AA-preferential 85 kDa cytosolic phospholipase A2 (cPLA2) from rabbit platelets in comparison with AA and eicosapentaenoic acid (EPA, 20:5(n - 3)) derivatives. When diacylGPE was used as a substrate, DHA release was almost negligible under the assay condition that allowed AA and EPA to be liberated at the rates of 4.3 mumol/min per mg protein and 2.5 mumol/min per mg protein, respectively. On the other hand, 14 kDa type II PLA2 hydrolyzed DHA-diacylGPE as well as AA-diacylGPE and EPA-diacylGPE. When DHA-diacylGPE and AA-diacylGPE were mixed at equimolar concentrations, DHA release by cPLA2 was not observed and AA release was reduced to 32% in the case without DHA-diacylGPE. This indicated that DHA-diacylGPE is a poor substrate but possesses the inhibitory activity for cPLA2. cPLA2 does not clearly discriminate between AA-alkenylacylGPE and AA-diacylGPE. As in the case using diacylGPE as a substrate, DHA-alkenylacylGPE was completely discriminated from AA-alkenylacylGPE by cPLA2. The roles of DHA and cPLA2 in the synthesis of lipid mediators will be discussed in relation to the new aspects of the substrate specificity of cPLA2 provided here.

Animals↗
PubMed1994

Colon cancer prevention with a small amount of dietary perilla oil high in alpha-linolenic acid in an animal model.

BACKGROUND: Epidemiologic and experimental studies suggest that dietary fish oil and vegetable oil high in omega-3 polyunsaturated fatty acids (PUFAs) suppress the risk of colon cancer. The optimal amount to prevent colon carcinogenesis with perilla oil high in omega-3 PUFA alpha-linolenic acid in a 12% medium-fat diet was investigated in female F344 rats. For comparison, safflower oil high in omega-6 PUFA linoleic acid was used. METHODS: Thirty or 25 rats at 7 weeks of age in each group received an intrarectal dose of 2 mg N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 and were fed the diets with various levels of perilla oil and safflower oil throughout the experiment. RESULTS: The incidence of colon cancer at the termination of the experiment at week 35 was 40%, 48% and 32% in the rats fed the diets with 3% perilla oil plus 9% safflower oil, 6% perilla oil plus 6% safflower oil, and 12% perilla oil plus 0% safflower oil, respectively, whereas it was 67% in the rats fed the control diet with 0% perilla oil plus 12% safflower oil. The amount of diet consumed and the body weight gain were identical in all of the dietary groups. The ratios of omega-3 PUFA to omega-6 PUFA in the serum and the colonic mucosa at week 35 were increased in parallel to the increased intake of perilla oil. CONCLUSIONS: The results suggest that a relatively small fraction of perilla oil, 25% of total dietary fat, may provide an appreciable beneficial effect in lowering the risk of colon cancer.

Animals↗
PubMed1994

Prevention of 1,2-dimethylhydrazine-induced colon tumorigenesis by HMG-CoA reductase inhibitors, pravastatin and simvastatin, in ICR mice.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin (Pr) and simvastatin (Si), suppressed 1,2-dimethylhydrazine (DMH)-induced colon cancer development in female ICR mice. All mice received an i.p. injection of 10 mg DMH/kg body wt once weekly for 15 weeks. Pr was administered at 0.01, 0.005 and 0.001% levels in drinking water, and Si at 0.01 and 0.002% levels in the diet. All animals had access to Pr or Si throughout the experiments which were terminated at weeks 25 or 30. Histologically most of the tumors were well-differentiated adenocarcinomas. The incidence of colon tumors examined at weeks 25 or 30 was reduced by 67% in the 0.01% Pr group, by 30% in the 0.005% Pr and 0.01% Si groups, and by 24% in the 0.001% Pr and 0.002% Si groups, compared with their respective controls. However, the differences did not reach statistical significance. The number of tumors per mouse was significantly reduced in all groups administered Pr and Si except the 0.001% Pr group as compared to their respective controls. The results from those three independent experiments seem to suggest that HMG-CoA reductase inhibitors may prevent colon tumorigenesis in laboratory animal model.

1,2-Dimethylhydrazine↗
PubMed1994

Phosphorylative inactivation of rifampicin by Nocardia otitidiscaviarum.

Rifampicin was inactivated by Nocardia otitidiscaviarum to yield two products designated RIP-3 and RIP-4. The full structures of RIP-3 and RIP-4 were determined to be 21-(O-phosphoryl) rifampicin and 3-formyl-21-(O-phosphoryl) rifamycin SV, respectively, but neither product had any antimicrobial activity.

Biotransformation↗
PubMed1994

alpha-Linolenic, eicosapentaenoic and docosahexaenoic acids affect lipid metabolism differently in rats.

Rats were fed purified diets containing 10% fat with constant (n-6):(n-3) polyunsaturated fatty acids [(n-6):(n-3); 2.3-2.6] and polyunsaturated:saturated fatty acids (1) ratios. This was obtained with alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid added at 1 g/100 g diet. Eicosapentaenoic acid and docosahexaenoic acid were added as the ethyl esters. The concentration of plasma cholesterol in rats fed docosahexaenoic acid was significantly lower than in those fed alpha-linolenic acid. The concentration of plasma triglyceride was significantly lower in rats fed eicosapentaenoic acid than in those fed docosahexaenoic acid. Docosahexaenoic acid significantly reduced hepatic cholesterol compared with alpha-linolenic acid and eicosapentaenoic acid. Both eicosapentaenoic acid and docosahexaenoic acid decreased hepatic triglyceride compared with alpha-linolenic acid, but this effect was more pronounced in the docosahexaenoic acid group. There was no significant difference in fecal excretion of neutral and acidic steroids and apparent fat absorption. In rats fed docosahexaenoic acid, the proportion of arachidonic acid in liver microsomal phosphatidylcholine was lower than in those fed eicosapentaenoic acid. The same tendency was observed in plasma, platelet and aortic phosphatidylcholine and liver microsomal phosphatidylethanolamine and phosphatidylinositol. Dietary docosahexaenoic acid, but not eicosapentaenoic acid, significantly decreased aortic production of prostacyclin compared to alpha-linolenic acid, whereas platelet aggregation by collagen was not affected by the difference in dietary (n-3) polyunsaturated fatty acids.

Animals↗
PubMed1994

Inactivation of the macrolide antibiotics erythromycin, midecamycin, and rokitamycin by pathogenic Nocardia species.

A survey of five Nocardia spp. with respect to susceptibility towards three macrolides (erythromycin, rokitamycin, and midecamycin) showed that the Nocardia spp. have different susceptibility profiles. Most of the resistance was due to the inactivation of the macrolides by phosphorylation, glycosylation, reduction, deacylation, or a combination thereof.

Biotransformation↗
PubMed1994

The effect of oral administration of eicosapentaenoic and docosahexaenoic acids on acute inflammation and fatty acid composition in rats.

To investigate effects of eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) on acute inflammation, we fed rats either of the following four diets: an EPA-rich diet for 5 or 15 days, a DHA-rich diet for 5 or 15 days, a control diet for 5 or 15 days, and standard chow for 15 days. At the end of diets, the carrageenan-induced swelling of footpads was measured. Peritoneal cells were analyzed for their fatty acids in the phospholipid fraction. The swelling was similarly reduced in the EPA and DHA groups (p < 0.05, if fed for 15 days) compared with rats fed the control diet for 15 days. The mean proportion of arachidonic acid (AA) to the sum of highly unsaturated fatty acids was correlated (r = 0.87) to the mean degree of swelling among all dietary groups (n = 7). Effects of EPA and DHA might be explained by the reduced availability of AA for eicosanoid formation represented by the proportion of AA.

Animals↗
PubMed1994

Three new reduced anthracycline related compounds from pathogenic Nocardia brasiliensis.

Three new metabolites were isolated from a pathogenic bacterium, Nocardia brasiliensis IFM 0075 strain, a producer of a new anthracycline antibiotic (SO-075R1) and its mutant strain (IFM 0075-13-1). The structural studies showed that they are reduced anthracyline related compounds. Some biosynthetic routes of these metabolites were discussed.

Anthracyclines↗
PubMed1993

Reduction in formation and growth of 1,2-dimethylhydrazine-induced aberrant crypt foci in rat colon by docosahexaenoic acid.

The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 times a week for 4, 8, or 12 weeks from the day before the first carcinogen treatment. The numbers of DMH-induced aberrant crypt foci per colon after 4, 8, and 12 weeks of DHA treatment were approximately 40% of those in the respective control groups, and the differences were statistically significant. The numbers of foci reached plateau levels at 8 weeks in both the DHA-treated and control groups. The mean number of aberrant crypts per focus was also significantly smaller in the group given DHA than that in the control group at each time. These results suggest that DHA suppresses the formation and growth of aberrant crypt foci and has a preventive effect on colon carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1993

Effect of docosahexaenoic acid on the generation of platelet-activating factor by eosinophilic leukemia cells, Eol-1.

Human eosinophilic leukemia (Eol-1) cells were examined for their ability to generate platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) (PAF) and the effect of supplementation of docosa-hexaenoic acid (C22:6n-3) (DHA) on the PAF synthesis was explored in relation to the fatty acid composition of phospholipids and the liberation of arachidonic acid (C20:4n-6 AA). Although undifferentiated cells did not produce PAF, the exposure of IFN-gamma differentiated Eol-1 to generate PAF in response to the Ca-ionophore. In addition, the IFN-gamma-treated cells acquired the ability to release free fatty acids, approximately 55% of which was found to be AA. When DHA was supplemented into the culture of Eol-1 for 24 h, PAF production decreased by 40 to 50% at concentrations of 3 to 10 microM. On the other hand, supplementation of 10 microM eicosapentaenoic acid (C20:5n-3) did not significantly decrease PAF production. With the supplementation of 10 microM DHA, DHA levels in phospholipid subclasses, including alkylacylglycerophosphocholine, were greatly increased with concurrent decreases in other unsaturated fatty acids. In these cells, the liberation of AA in response to an ionophore was decreased by 55%. Even when DHA was enriched in phospholipids, DHA release in response to ionophore stimulation was almost negligible, indicating that the DHA moiety of phospholipids is not susceptible to the action of phospholipase A2. Furthermore, DHA supplementation appeared to attenuate phospholipase A2 reaction by some unknown mechanism because the decrease in AA release was much more than that for the AA level in phospholipids. Acetyl-CoA:1-alkylGPC acetyltransferase activity of stimulated cell lysate was also reduced by DHA supplementation but the reduction was much less when compared with that of PAF synthesis or AA release. These results implicated that enrichment of DHA attenuates enzymic reactions for PAF synthesis, mainly the initial reaction catalyzed by AA-specific phospholipase, and thereby reduces PAF synthesis in Eol-1.

Acetyltransferases↗
PubMed1993

Lymphatic transport of eicosapentaenoic and docosahexaenoic acids as triglyceride, ethyl ester and free acid, and their effect on cholesterol transport in rats.

Lymphatic transport of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids given in the forms of triglyceride, ethyl ester of free acid and their effect on cholesterol transport was compared in lymph-cannulated rats. Lymphatic recovery of DHA and EPA given by stomach tube in the form of triglyceride in which they were mainly located at the 2-position was significantly higher than that of the ethyl ester or free acid during the first 6 hr after the administration and the tendency continued until 9 hr. In contrast, the 9 to 24 hr recovery of DHA and EPA in the forms of ethyl ester and free acid was considerably higher than that of triglyceride. Consequently, cumulative 24 hr recovery of EPA was comparable among the three forms. However, the 24 hr recovery of DHA was highest in free acid, lowest in ethyl ester and intermediate in triglyceride. Recovery of the free acid between 9 and 24 hr after administration was significantly higher than that given in the forms of triglyceride or ethyl ester. Cholesterol recovery in lymph of rats given with ethyl ester or free acid was lower than that given with triglyceride at an early stage after the administration in both EPA and DHA. Cumulative 24 hr recovery of cholesterol in rats given these fatty acids as ethyl ester was significantly lower than in those given as the other two forms.

Animals↗
PubMed1993

Modulation by histamine of the delayed outward potassium current in guinea-pig ventricular myocytes.

1. Histamine receptor-mediated modulation of the delayed outward potassium current (IK) was investigated in guinea-pig single ventricular cells by the whole-cell voltage clamp. 2. Histamine increased IK in a dose- dependent manner with a half-maximum dose of 3.8 x 10(-8) M. Histamine (10(-6) M) increased IK by a factor of 3.02 without a significant change in the current kinetics. The threshold dose of histamine for increasing IK was 10(-9) M and this value was similar to that for calcium current. 3. Cimetidine decreased IK in the presence of histamine, by shifting the dose-response curve to histamine to the right. The pA2 value of cimetidine against histamine was 6.38. 4. Forskolin did not increase IK after application of 10(-6) M histamine, and histamine scarcely increased IK in the presence of a heat-stable inhibitor of cyclic AMP-dependent protein kinase (PKI). 5. We conclude that stimulation by histamine of IK is mainly by way of the H2-receptor, and is mediated by cyclic AMP-dependent phosphorylation.

Animals↗
PubMed1993

Inactivation of rifampin by Nocardia brasiliensis.

Rifampin was glycosylated by a pathogenic species of Nocardia, i.e., Nocardia brasiliensis. The structures of two glycosylated compounds (RIP-1 and RIP-2) isolated from the culture broth of the bacterium were determined to be 3-formyl-23-(O-[beta-D-glucopyranosyl])rifamycin SV and 23-(O-[beta-D-glucopyranosyl])rifampin, respectively. Both compounds lacked antimicrobial activity against other gram-positive bacteria as well as the Nocardia species.

Glycosylation↗
PubMed1993

Intravenous infusion of tridocosahexaenoyl-glycerol emulsion into rabbits. Effects on leukotriene B4/5 production and fatty acid composition of plasma and leukocytes.

Leukotriene (LT) B4 is a major chemical activator of PMN. Inhibitory effects of oral administration of docosahexaenoic acid (DHA) on LTB4 synthesis by PMN are known. We intravenously infused tridocosahexaenoyl-glycerol (DHA-TG) emulsion into rabbits in three different doses, namely 0.8, 0.4, or 0.2 g DHA/kg, and investigated the changes in LTB4/5 production by ionophore-activated PMN. The averaged LTB4 production by PMN was significantly reduced to 57 and 59% of baseline at 6 h after the infusion of 0.8 and 0.4 g DHA/kg, respectively (P < 0.05), but not after the infusion of 0.2 g DHA/kg or 0.8 g soybean oil/kg. The combined concentrations of both DHA and eicosapentaenoic acid in the PMN phospholipid fraction were significantly increased at 6 h after the infusion of 0.8 or 0.4 g DHA/kg but not after the infusion of 0.2 g DHA/kg or 0.8 g soybean oil/kg. Oral administration of 0.8 g DHA/kg did not increase DHA or eicosapentaenoic acid in the PMN phospholipid fraction and did not decrease LTB4 production by PMN at 6 h after administration. We suggest that the infusion of 0.4-0.8 g DHA/kg might be beneficial to patients who suffer from diseases that are related to the acute elevation of LTB4 production.

Animals↗
PubMed1993

Stimulation of nerve growth factor synthesis and secretion by fellutamide A in vitro.

Fellutamide A, a tripeptide derivative from Penicillium fellutanum was found to be a potent enhancer of nerve growth factor (NGF) synthesis and secretion in vitro. This compound enhanced production of NGF in L-M cells, rat brain cells, and rat glial cells. The mode of action of this compound was suggested to be different from that of a known NGF inducer, epinephrine, as inducing activities of fellutamide A and epinephrine were additive when they were admixed at the concentration which gave saturation in its respective activity. Furthermore, fellutamide A but not epinephrine induced production of NGF in the rat brain cells. NGF-inducing activity of several tripeptides and other compounds related to fellutamide A was examined.

Amino Acid Sequence↗
PubMed1993

Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C.

The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC-14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 micrograms/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 micrograms/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 micrograms/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA-VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA-VC.

Ascorbic Acid↗
PubMed1993

Inactivated products of rifampicin by pathogenic Nocardia spp.: structures of glycosylated and phosphorylated metabolites of rifampicin and 3-formylrifamycin SV.

Rifampicin (1) was converted into four inactivated products by pathogenic Nocardia, RIP-1 and RIP-2 by N. brasiliensis and RIP-3 and RIP-4 by N. otitidiscaviarum. MS and NMR analysis showed the compounds to be 3-formyl-23-[O-(beta-D-glucopyranosyl)]rifamycin SV (2), 23-[O-(beta-D-glucopyranosyl)]rifampicin (3), 21-(O-phosphoryl)rifampicin (4) and 3-formyl-21-(O-phosphoryl)-rifamycin SV (5), respectively.

Drug Resistance↗